That Neuroscience Guy - The Neuroscience of Placebos

Episode Date: April 9, 2026

In today's episode of That Neuroscience Guy, we discuss the neuroscience behind placebo treatments. 

Hi, my name's Olive Kirk Olson, and I'm a neuroscientist at the University of Victoria. And in my spare time, I'm that neuroscience guy. Welcome to the podcast. During World War II, a young anesthesiologist named Henry Beecher was working in a field hospital treating wounded soldiers. Supplies were limited, and one day the hospital ran out of morphine, the main painkiller used during surgery. A severely injured soldier needed treatment. but there was just no anesthetic left. One of the nurses had an idea.

She filled a syringe with saline, basically salt water, and injected it into the soldier while telling him it was morphine. Something remarkable happened. The soldier relaxed. His pain decreased enough that the doctors were able to proceed with the procedure. Beecher later realized something important. The relief wasn't coming from the drug. There was no drug.

It was coming from the belief that the drug had been given. That observation helped introduce the modern scientific concept of the placebo effect, and it revealed something fascinating about the brain. What we expect to happen can dramatically change how our bodies actually feel. On today's podcast, the placebo effect. Placebo effects are often misunderstood. People assume placebo responses are imaginary, psychological tricks. people convincing themselves that they feel better. But research shows the changes are biologically real. Brain imaging studies demonstrate measurable changes in neural activity during placebo responses.

Basically, the big idea is that the brain doesn't passively experience the body. It actively interprets and regulates body signals. So our experience of symptoms is influenced by sensory, signals from the body, prior experience, your memory, right? That influences what you expect you should feel. And it's learned. And our expectations about what should happen. And when those expectations shift, the brain can change how symptoms are processed. So in the placebo effect, positive expectations reduce symptoms. That's the example from the top of the podcast. When the soldier was given the fake morphine, they expected the pain to go away. And there's the nocebo effect,

which is the opposite. Negative expectations increase symptoms. A good example of that, again, stems from medicine. If a patient is told that a medication might cause nausea or headaches, those symptoms appear far more often, even when the pill contains no active drug. Do you see how the negative expectation there, you know, activates those symptoms. So that is the placebo and the nocebo effect. Now, the placebo and nocebo effects involve specific brain mechanisms. Basically, they're highly tied to the pain regulation networks. And the most common brain regions in the pain regulation networks are old friend the anterior cingulate cortex, which is well known, known for the way it controls the brain and regulates the brain. The prefrontal cortex, of course,

which is a big part of our belief system. So if you think of the placebo and the nocebo effects, it's the prefrontal cortex that generates and brings together the beliefs that we feel. The insula for its well-known role in emotion and also the amygdala as well, of course. Now, these are the brain regions involved in the top-down control of pain. signals. Now, let's just review what I mean by top-down control. We've talked about it before, but top-down control is basically the concept that the higher levels of the brain can exert control over lower parts of the brain, or the nervous system, or the body. So the idea is that these brain regions, they can down-regulate the sensation of pain. That's top-down control. The brain can

literally adjust how strongly pain is experienced. Now, that's not the only brain system that's involved in the placebo effect. There's something called the endogenous opioid system. It's one of the clearest mechanisms that lies behind placebo pain relief. When people experience relief, because they expect it, the brain releases its own opioid chemicals. So there's research that proves this. If researchers give participants something called naloxone, which blocks opioid receptors, placebo pain relief is greatly reduced.

So you can run this as a study, and that's what they did. They basically blocked the brain's ability to release the opioids, and as a result, the pain relief from the placebo effect was reduced. And what that means is, that the brain is producing its own pain relieving chemistry, which is kind of cool. The brain can control how you experience pain.

Now, remember that the way pain is normally experienced is that something happens to the body. In the case of our soldier and our example in the front end, well, he was in pain because he was hurt. But the brain has its ability to control just how much you experience that pain. Now there are other brain circuits that are involved in the placebo effect and the nocebo effect. There's the dopamine and reward systems. Basically, expectations of improvement, so the idea that the placebo can help you can activate the dohemine system in the brain. And we know that the dohamine system can modulate body function. For example, in Parkinson's disease research, placebo treatments can temporarily increase dohemine activity.

and they actually improve motor function. So belief can trigger real neurochemical changes. And there's also an aspect of learning and conditioning. Some placebo responses are basically conditioned, like classical conditioning rather than conscious belief. So, for instance, if someone repeatedly takes a medication that reduces symptoms, the brain learns to associate the context of the treatment with relief. eventually the treatment ritual itself can trigger part of the response.

Do you get what I mean there? Basically, the process of the treatment is a trigger which triggers this placebo-like symptom. So one of the most famous studies with the placebo effect involves knee surgery for arthritis. Researchers at the Baylor College of Medicine wanted to know how much of the surgical belief and benefit came from the procedure itself. So they designed a control study. Some patients received the full surgery. Others received only partial elements of the surgery.

Now, as a researcher, I'm not sure how they pulled this off. A third group received sham surgery. The surgeons made incisions in the knees to simulate the operation, but they did not perform the surgical repair. All patients believed they had received the real procedures. Months later, the researchers evaluated the outcomes. pain levels improved, mobility improved, quality of life improved, but here's the surprising result. Patients in the sham surgery group, so people that didn't even get operated on, but it looked like they had,

improved just as much as the patients who had had the real operation. In other words, a large portion of the benefit appeared not to come from the surgery itself, but from the expectation that the surgery would work. and this was a powerful demonstration of how strongly belief can influence physical experience. Now, of course, this was a controlled study in a research environment. And another thing is you can't placebo yourself, right? You have to believe what's happening. What I mean by that is you couldn't, like if you need knee surgery, don't cut your knee a few times

and believe that you've had knee surgery. It doesn't work that way. The reason the sham group believed it is because they were in a hospital and they They went through the full surgical procedure, and when they woke up, they had, you know, what looked like surgery being done to their knee. But you can't do it to yourself. That's the take-home warning message. Now, there's some interesting everyday applications of the placebo effect. So medication side effects.

In many drug trials, a significant portion of reported side effects occurred in the placebo group. People experienced symptoms simply because they were warned those symptoms. might occur. That's the nocebo effect. All right? So if you think about it, if you watch television here in North America, there's all these warnings about these pills and all the side effects, they're actually setting you up for the nocebo effect in the sense that if you see that those are side effects and you believe that those are side effects, they might end up being worse than the actual side effects. You can see it with supplements and wellness products. people often report these dramatic improvements from supplements with limited scientific evidence.

Expectations alone can influence perceived energy, pain levels, mood, concentration. Remember, belief interacts with real brain systems. You know, another example of this. I read it online and then I felt it. Information can shape your expectations. If people read about a possible symptom, they may begin paying more attention to bodily sensations. Normal sensations can subtly feel meaningful or concerning. Think of the COVID pandemic.

We had all heard about the COVID symptoms, and a lot of the people I know were wandering around thinking they had COVID because they'd been told about these symptoms and all of a sudden anything they felt was interpreted as a COVID symptom. expectation shapes interpretation. Now there's ways you can harness the placebo ethically. The goal isn't deception, but research has shown that clinicians can improve outcomes by shaping expectations honestly. For instance, explaining treatments clearly and confidently,

emphasizing recovery potential, as opposed to the negative side, creative supportive treating environments. So even open-labeled placebos, where patients know the pill contains no active drug, can still produce improvements. Expectations alone can influence physiology. The placebo and nocebo effects remind us that our experiences of the body is not just a direct readout of physical signals. It's shaped by learning, context, attention, and most importantly, belief.

The brain doesn't simply detect symptoms. In many cases, it helps create the experience. of those symptoms. And that means the way we think about treatments, health, and recovery can genuinely influence how we feel. So I hope you enjoyed that run-through of the placebo and nocebo effects. Don't forget the website. That Neuroscience Guy.com links to Etsy,

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